Inactivated Poliomyelitis Vaccine Research Articles

A phase 3 randomized, open-label study evaluating the immunogenicity and safety of concomitant and staggered administration of a live, pentavalent rotavirus vaccine and an inactivated poliomyelitis vaccine in healthy infants in China

ABSTRACT This open-label, randomized, phase 3 study in China (V260-074; NCT04481191) evaluated the immunogenicity and safety of concomitant and staggered administration of three doses of an oral, live, pentavalent rotavirus vaccine (RV5) and three doses of an intramuscular, inactivated poliomyelitis vaccine (IPV) in 400 healthy infants. The primary objective was the non-inferiority of neutralizing antibody (nAb) responses in the concomitant- versus the staggered-use groups. Antibody responses were measured at baseline and 1-month post-dose 3 (PD3). Parents/legal guardians recorded adverse events for 30 or 15 d after study vaccinations in the concomitant-use or staggered-use groups, respectively. At PD3, >98% of participants seroconverted to all three poliovirus types, and the primary objective was met as lower bounds of the two-sided 95% CI for between-group difference in nAb seroconversion percentages ranged from − 4.3% to − 1.6%, for all poliovirus types, p < .001. At PD3, geometric mean titers (GMTs) of nAb responses to poliovirus types 1, 2, and 3 in the concomitant-use group and the staggered-use group were comparable; 100% of participants had nAb titers ≥1:8 and ≥1:64 for all poliovirus types. Anti-rotavirus serotype-specific IgA GMTs and participants with ≥3-fold rise in postvaccination titers from baseline were comparable between groups. Administration of RV5 and IPV was well tolerated with comparable safety profiles in both groups. The immunogenicity of IPV in the concomitant-use group was non-inferior to the staggered-use group and RV5 was immunogenic in both groups. No safety concerns were identified. These data support the concomitant use of RV5 and IPV in healthy Chinese infants.

Quantitative Analysis of the Instant and Persistent Inhibition Effects of Maternal Poliovirus Antibodies on the Immune Response in a Phase IV Trial of a Sabin Strain-Based Inactivated Poliovirus Vaccine.

An inactivated poliomyelitis vaccine made from Sabin strains (sIPVs) has widely been used in China since 2015. However, the quantitative data on the instant and persistent inhibition effects of maternal poliovirus antibodies on the immune response to sIPV priming and booster vaccination have not been available yet. In this study, we aim to explore and quantify the instant and persistent inhibition effect of maternal poliovirus antibodies on the immune response elicited by sIPV primary and booster vaccination. The immunogenicity data consisting of the days 0 and 30 after the prime and booster vaccination of the sIPV in a phase IV trial were pooled for a quantitative analysis of the inhibition effect of maternal poliovirus antibody. The geometric mean ratio (GMR) was calculated using linear regression models, representing that every 2-fold higher maternal poliovirus antibody titer may result in a (1-GMR) lower postimmunization antibody titer. The GMRs for poliovirus types 1, 2, and 3 were 0.79 (0.77-0.82), 0.85 (0.81-0.89), and 0.87 (0.83-0.91) at 30 days after the priming series, 0.86 (0.83-0.89), 0.81 (0.76-0.85), and 0.86 (0.80-0.93) at one year after the priming series, and 0.96 (0.94-0.99), 0.89 (0.86-0.93), and 0.98 (0.93-1.03) at 30 days after the booster dose. The inhibition effect continued to exist until the booster dose 1 year later, and such a persistent inhibition effect was almost attenuated for poliovirus types 1 and 3, and partly reduced for type 2 at 30 days after the booster dose. A wider interval between the four sIPV doses might be a consideration for reducing the effect of maternal antibodies and subsequently eliciting and maintaining higher antibody levels to protect against poliovirus transmission and infection at the final stage of polio eradication in the global world. This study's clinical trial registry number is NCT04224519.

Comparison between recommended and mandatory vaccine uptake during adolescence in Italy

Abstract Background Immunization programs are key preventive interventions and have largely contributed to reducing the burden of infectious diseases and decreasing related morbidity, mortality and healthcare costs. The study aimed to investigate coverage regarding diphtheria, tetanus, and acellular pertussis (dTap) - Inactivated Poliomyelitis Vaccine (IPV) and Human Papilloma Virus (HPV) vaccine and attitudes towards vaccinations among undergraduate university students in Southern Italy. Methods This cross-sectional study was conducted among 327 students through an anonymous online questionnaire and included socio-demographic characteristics, attitudes towards vaccinations overall and specifically on dTap-IPV and HPV, reasons for having received or not vaccinations and willingness to receive vaccinations. Results One third of the students were concerned about serious adverse effects of vaccines and 95% believed that vaccines for uncommon diseases are useless. During adolescence, 89% of the sample received the mandatory dTap-IPV vaccine booster. Among unvaccinated students, 45% were unwilling to get vaccinated against dTap-IPV because they believed not to be at risk of infection (59%) and had lack of recommendation (35.3%). Regarding vaccination against HPV, 67% had received the recommended schedule. Among those who did not receive it, 34% were unwilling to get vaccinated because they did not feel at risk of HPV infection (41%). Interestingly, 16% of the sample disclosed some barriers to access vaccination centers. Moreover, 30% declared that HPV vaccination was discouraged by healthcare professionals (HCPs). Conclusions Vaccination uptake is worryingly low and national objective coverage seems not still achieved. Likewise, risk perception of vaccine-preventable diseases was low and it seems negatively impact on the intention to get vaccinated. Improving vaccine confidence among HCPs is crucial as they have been shown to have the potential to influence patient vaccination uptake. Key messages

Safety evaluation on concomitant immunization with inactivated poliomyelitis vaccine produced from Sabin strains and other vaccines (from 2015 to 2020)

ABSTRACT Objective To evaluate the safety of concomitantly administering inactivated poliomyelitis vaccine produced from Sabin strains (sIPVs) with other vaccines. Methods A descriptive analysis was carried out on adverse events following immunization (AEFI) based on the administration of sIPV alone or concomitant with other vaccines (from 2015 to 2020) using data from the national AEFI surveillance system of China (CNAEFIS). All adverse reactions (ADRs) of the concomitant immunization were coded using a medical dictionary for regulatory activities (MedDRA) before comparison. Results The CNAEFIS reported a total of 9130 sIPV-related AEFI cases, including 6842 AEFI cases collected after immunization with sIPV alone and 2288 AEFI cases collected after immunization of sIPV concomitant with other vaccines. The combination of sIPV with diphtheria, tetanus and pertussis vaccine (DTaP) was correlated with the highest frequency of AEFI, which accounted for 53.50% of all 2288 AEFI cases. After MedDRA-based coding, the most frequent ADR was fever (70.18%), followed by erythema and swelling at the injection site (6.95%), induration at the injection site (3.85%), dermatitis allergy (3.56%) and urticaria (1.55%). A statistically significant difference (P < .001) was found between sIPV immunization and sIPV immunization concomitant with other vaccines for general reactions (95.36% and 93.22%, respectively) and abnormal reactions (4.64% and 6.78%, respectively). Conclusion No new safety signal is found for sIPV administered concomitantly, although its administration with other vaccines may increase the occurrence of abnormal reactions. Vaccine manufacturers should focus on the safety of administering sIPV with DTaP and carry out relevant clinical studies when necessary.

The COVID-19 pandemic and vaccination abandonment in children: spatial heterogeneity maps.

Objective: to identify spatial clusters corresponding to abandonment of routine vaccines in children.Method: an ecological study, according to data from the 853 municipalities of a Brazilian state. The records analyzed were those of the multidose pentavalent, pneumococcal 10-valent, inactivated poliomyelitis and oral human rotavirus vaccines of 781,489 children aged less than one year old. The spatial scan statistics was used to identify spatial clusters and assess the relative risk based on the vaccination abandonment indicator.Results: the spatial scan statistics detected the presence of statistically significant clusters for abandonment regarding the four vaccines in all the years analyzed. However, the highest number of clusters with high relative risk estimates was identified in 2020. The Vale do Aço and West, North and West, and Southwest regions stand out for the pentavalent, poliomyelitis and rotavirus vaccines, respectively.Conclusion: in an attempt to mitigate the devastating impact of the COVID-19 pandemic, the immunization program experienced setbacks. The presence of clusters points to the need to implement integrated strategies that may involve different sectors for an active search for children and prevent outbreaks of vaccine-preventable diseases in the near future.

Immunogenicity of fractional-dose of inactivated poliomyelitis vaccine made from Sabin strains delivered by intradermal vaccination in Wistar rats

Reducing the amount of antigen is an important strategy to resolve the present shortage of IPV supply for global polio eradication. In the study, we compared the immunogenicity of adjuvanted and non-adjuvanted fractional-dose of IPV made from Sabin strains (sIPV) by intradermal (ID) administration versus the full-dose of sIPV by intramuscular (IM) administration in rats by comparing seroconversion rates and geometric mean titers (GMTs) of neutralizing antibodies (NAbs). We found that, after the full 0, 1, 2 months schedule immunizations, the seroconversion rates in all groups reached 100% except non-adjuvanted 1/6 dose group. After 2 immunizations, the seroconversion rates in all the adjuvanted fractional-dose groups and the full-dose group reached 100%. The GMTs of NAbs induced by adjuvanted 1/12 fractional-dose and full-dose of sIPV were similar and dynamics of the antibody responses were consistent. We proves that the Th1/Th2 balance was not changed by the administration route by comparing ratios of the IgG subclass. Our study confirms that ID administration could reduce the required amount of antigens, the adjuvanted fractional-dose resulted in earlier and higher antibody response for all serotypes than that of non-adjuvanted fractional-dose, and the NAbs responses elicited by 1/12 dose was comparable to that by full-dose of sIPV.

Establishment of the 1st National Reference Standard for Sabin Inactivated Poliomyelitis Vaccine in Korea

In 2019, the first Sabin strain inactivated poliomyelitis vaccine was approved in Korea. It was necessary establishment of national reference standards of that vaccine for consistent quality control and standardization since international standards are provided only in small quantities per year. Therefore, Sabin strain inactivated poliomyelitis vaccine standard candidate was produced in 2019. In this study, we tried to establish the D-antigen content of the candidate standard through collaborate study with five institutions and six laboratories participated in the collaborate research. The candidate standard was set up value of DU/mL with Salk strain International Standard (12/104, NIBSC) and the SDU/mL value was established with the Sabin International Standard (17/160, NIBSC). The D-Ag contents (DU/mL and SDU/mL) derived from each laboratory were calculate using the CombiStat program and analyzed for statistical significance. Earlier this year, the candidate standard was registered as the 1st national reference standard of Sabin strain inactivated poliomyelitis vaccine and the D-Ag contents of the standard was assigned 47, 129, 262 DU/mL and 48, 106, and 193 SDU/mL by ​each type (Type 1, 2, 3,). Because of established of national standard, it will help consistent quality control and standardization of the Sabin strain inactivated poliomyelitis vaccines.

Characterization of Classical Vaccines by Charge Detection Mass Spectrometry.

Vaccines induce immunity by presenting disease antigens through several platforms ranging from individual protein subunits to whole viruses. Due to the large difference in antigen size, the analytical techniques employed for vaccine characterization are often platform-specific. A single, robust analytical technique capable of widespread, cross-platform use would be of great benefit and allow for comparisons across manufacturing processes. One method that spans the antigen mass range is charge detection mass spectrometry (CDMS). CDMS is a single-ion approach where the mass-to-charge ratio (m/z) and charge are measured simultaneously, allowing accurate mass distributions to be measured for heterogeneous analytes over a broad size range. In this work, CDMS was used to characterize the antigens from three classical multivalent vaccines, inactivated poliomyelitis vaccine (IPOL), RotaTeq, and Gardasil-9, directly from commercial samples. For each vaccine, the antigen purity was inspected, and in the whole virus vaccines, empty virus particles were detected. For IPOL, information on the extent of formaldehyde cross-linking was obtained. RotaTeq shows a narrow peak at 61.06 MDa. This is at a slightly lower mass than expected for the double-layer particle, suggesting that around 10 pentonal trimers are missing. For Gardasil-9, buffer exchange of the vaccine resulted in very broad mass distributions. However, removal of the virus-like particles from the aluminum adjuvant using a displacement reaction generated a spectrum with narrow peaks.

Immunogenicity and Safety of Inactivated Sabin-Strain Polio Vaccine “PoliovacSin”: Clinical Trials Phase I and II

Global polio eradication requires both safe and effective vaccines, and safe production processes. Sabin oral poliomyelitis vaccine (OPV) strains can evolve to virulent viruses and result in poliomyelitis outbreaks, and conventional inactivated poliomyelitis vaccine (Salk-IPV) production includes accumulation of large stocks of neurovirulent wild polioviruses. Therefore, IPV based on attenuated OPV strains seems a viable option. To increase the global supply of affordable inactivated vaccine in the still not-polio free world we developed an IPV made from the Sabin strains–PoliovacSin. Clinical trials included participants 18–60 years of age. A phase I single-center, randomized, double-blind placebo-controlled clinical trial included 60 participants, who received one dose of PoliovacSin or Placebo. A phase II multicenter, randomized, double-blind, comparative clinical trial included 200 participants, who received one dose of PoliovacSin or Imovax Polio. All vaccinations were well tolerated, and PoliovacSin had a comparable safety profile to the Placebo or the reference Imovax Polio preparations. A significant increase in neutralizing antibody levels to polioviruses types 1–3 (Sabin and wild) was observed in PoliovacSin and Imovax Polio vaccinated groups. Therefore, clinical trials confirmed good tolerability, low reactogenicity, and high safety profile of the PoliovacSin and its pronounced immunogenic properties. The preparation was approved for clinical trials involving infants.

Immunogenicity and safety of the inactivated poliomyelitis vaccine made from Sabin strains in a phase IV clinical trial for the vaccination of a large population

As a recently launched novel vaccine used as one of the vaccines for the final eradication of polios worldwide, complete data on the consistency and immunogenicity characteristics of the inactivated poliomyelitis vaccine made from the Sabin strain (sIPV) and its safety in large-scale populations are required to support the future use of this vaccine worldwide. A phase IV clinical trial was conducted to perform an immunogenicity evaluation of lot-to-lot consistency of three commercial batches of sIPV in 1200 infants and to investigate the vaccine’s safety on a large-scale in 20,019 infants for active monitoring and 29,683 infants for passive monitoring through the Adverse Event Following Immunization (AEFI) reporting system in China. In the immunogenicity evaluation, the average seroconversion rates for type I, type II and type III of the three groups were 99.83%, 98.93% and 99.44%, respectively. No differences in the seroconversion rate and the GMT ratios were noted in the pair-to-pair comparisons. In the large-scale safety evaluation, most adverse reactions occurred 0–30 days after the first doses, and the common local and systemic reactions were similar to those in the phase III clinical trial, with low incidence in both activated and passive monitoring. In conclusion, sIPV exhibits good lot-to-lot consistency and safety in large-scale populations; thus, it is qualified to serve as one of the vaccines for use in eradicating all wild and vaccine-derived polioviruses worldwide in the near future.Clinic Trial Registration. NCT04224519 and NCT04220515.

Polio vaccination coverage among children aged 12-23 months in a health block in North Kerala

Background: Polio (poliomyelitis) is a highly infectious viral disease which affects the nervous system and can result in irreversible paralysis within hours. There is no cure for polio, hence it becomes necessary to prevent the disease through vaccination. Thus, the objective of this study was to evaluate the polio vaccination coverage among children aged 12-23 months in a health block in Kannur, North Kerala.Methods: A community based cross sectional study was conducted among the children in the age group of 12-23 months residing in Pappinisseri block of Kannur district. Stratified random sampling was used. The details of 321 children were obtained using a pre-tested semi-structured questionnaire. The data was entered into Microsoft Excel 2007 spread sheet and analyzed using SPSS version 16.0 software.Results: Of the 321 children, males constituted 173 (54%) and females constituting 148 (46%). The total coverage of oral polio vaccines (OPV) (considering OPV-0, 1st, 2nd and 3rd doses) was found to be 92.8% and the inactivated poliomyelitis vaccine (IPV) coverage (IPV 1st and 2nd doses) to be 90.7%. Also, majority of the respondents were unaware of the use of OPV and IPV vaccines in the UIP.Conclusions: In spite of the efforts taken by the Government and the health officials, the OPV and IPV coverage has not reached 100% and also, the knowledge of mothers regarding the diseases prevented by the vaccines were very low. The reasons for this needs to be further evaluated.

Consistency Study for Three Commercial Lots of Inactivated Poliomyelitis Vaccine Made From Sabin Strain

Consistency Study for Three Commercial Lots of Inactivated Poliomyelitis Vaccine Made From Sabin Strain

Analysis on the characteristics of suspected vaccine-related deaths in Fujian Province, 2012-2017

Objective: To analyze the characterisitics of the death cases suspected to be related to vaccination in Fujian Province from 2012 to 2017. Methods: A total of 33 death cases information which was suspected to be related to the vaccinations from 2012 to 2017 were extracted from Chinese Adverse Events Following Immunization Information System (AEFI). The autopsy reports and the conclusions made by AEFI investigation diagnosis expert committee were collected at the same time. The inoculation data were obtained through the Fujian province Immunization Program Information System. The AEFI incidence, rare vaccine reaction incidences and mortality rates following immunization were figured out to analyze the characterisitics of the death cases associated with vaccination. Results: The age of deuths cases was from 26 days to 52 months. Among 33 cases, 23 were males, and 8 were due to vaccine-related reaction, and the others were due to coincidental events. The number of rare vaccine reaction cases from 2012 to 2017 were 2,3,6,8,7 and 7, respectively. The highest AEFI incidence was measles and rubella combined attenuated live vaccine [38.88 (95%CI: 36.85-40.91)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [2.01 (95%CI: 1.73-2.30)/100 000 dose]. The highest rare vaccine reaction incidence was measles and rubella combined attenuated live vaccine [15.04 (95%CI: 13.78-16.30)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [0.38 (95%CI: 0.25-0.50)/100 000]. The highest mortality rate was inactivated poliomyelitis vaccine [0.26 (95%CI: 0.04-0.54)/100 000 doses], and the lowest mortality rate was measles, mumps and rubella combined attenuated live vaccine [0.01 (95%CI: 0.00-0.08)/100 000 doses]. The Spearman correlation analysis showed that there were correlations between AEFI incidence and rare vaccine reaction incidence (r=0.64, P=0.048), there were no correlations between AEFI incidence and mortality rate (r=-0.34, P=0.329), and there were no correlations between rare vaccine reaction incidence and mortality rate (r=-0.25, P=0.484). Conclusion: Neither AEFI incidence nor rare vaccine reaction incidence was correlation with mortality rate. The main causes of death following vaccination were coincidental events.

Immunogenicity analysis of sequential inoculation of different strains of poliomyelitis vaccines in Shanghai

Objective: To evaluate the immunogenicity of different strains of inactivated poliomyelitis vaccines (IPV) by sequential program. Methods: This parallel-group controlled trial was conducted in immunization clinics in Shanghai from March 2016 to September 2017. Sabin strains inactivated poliomyelitis vaccines (sIPV), WPV strains inactivated poliomyelitis vaccines (wIPV) and live poliomyelitis Type Ⅰ Type Ⅲ vaccine (bOPV) as the investigational vaccine were used at 2, 3, 4 months old in 325 infants in Shanghai. Infants vaccinated by four sequential program were divided into 4 groups: sIPV+sIPV+bOPV, sIPV+wIPV+bOPV, wIPV+sIPV+bOPV and wIPV+wIPV+bOPV. A total of 230 investigators' blood samples were collected before primary immunization and 163 investigators' blood samples were collected after primary immunization. A total of 151 investigators (36, 44, 30 and 41 in each group) finished primary immunization and blood sampling before and after the primary immunization. The geometric mean titer (GMT) of poliovirus typesⅠ and Ⅲ neutralizing antibody was tested and calculated, and the positive results of antibody before and after primary immunization were analyzed. Results: Among the 151 investigators, the age were (2.27±0.61) months and birth weight were (3.27±0.43) kg, and 70 were male. The positive rates of typeⅠwas 98.68% (149 cases), and type Ⅲ was 97.35% (147 cases); the number of investigators tested in each group was 36, 44, 30 and 41, respectively; the positive rates of typeⅠwas 97.22% (35 cases), 100.00% (44 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.345); the positive rates of type Ⅲ were 97.22% (35 cases), 95.45% (42 cases), 96.67% (29 cases) and 100.00% (41 cases) (P=0.614). Conclusion: Using sIPV and wIPV simultaneously or alternately for sequential immunization of poliomyelitis vaccines showed good immunogenicity for infants at appropriate age.

Remarks on the possibility of introducing the fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule.

Given that the last notified case of poliomyelitis due to wild poliovirus type 2 was in 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of a bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported a reduction of the global supply of IPV. In response to the potential shortage of IPV, at a meeting held on March 10 2017, the SAGE and Technical Advisory Group (TAG) of the Pan American Health Organization (PAHO) urged the countries in the Latin American region to replace the routine administration of the full doses of inactivated polio vaccine (IPV-C) in the immunization schedule (administered by intramuscular route), administering a fraction of the full dose in two intradermal shots (IPV-f). The possibility of this strategy was analyzed by opinion leaders convened by the Paraguayan Society of Pediatrics with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). This document presents the results of the discussion.

Evaluation of the genetic stability of Sabin strains and the consistency of inactivated poliomyelitis vaccine made from Sabin strains using direct deep-sequencing

Inactivated poliomyelitis vaccine made from Sabin strains (sIPV) has been encouraged to introduce in the “Global Polio Eradication & Endgame Strategic Plan” and increasingly used worldwide. Attenuated Sabin strains used in manufacture of oral poliovirus vaccine (OPV) and sIPV may regain full or partial neurovirulence during growth in vaccine recipients and the vaccine manufacturing processes. Ensuring the molecular consistency of sIPV batches and that no mutation accumulates beyond the level present in past batches are important for quality control of vaccine manufacture process. Direct deep-sequencing allows the construction of a library of virus RNA and the detection of genetic mutations throughout the viral genome. In the present study, direct deep-sequencing was conducted to detect molecular mutations in virus passages, multiple sIPV monovalent lots, and virus monovalent lots from different polio type III strains. The results indicated that direct deep-sequencing can be used to identify and quantify small amounts of mutant viruses in vaccine preparations, trace the source of a specific virus seed, and monitor the batch-to-batch consistency of vaccines, suggesting that this technique could be suitable for the quality control and consistency monitoring of sIPV production.

Remarks on the possibility of the introduction of fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule

As last notified case of poliomyelitis due to wild poliovirus type 2 was 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported reduction in IPV global supply. In response to the possible shortage of IPV, the SAGE and Technical Adviser Group (TAG) of the Pan American Health Organization (PAHO), in the meeting of March 10, 2017, has urged that countries in the Latinamerican region should replace the routine administration of the full doses of polio inactivated vaccine (IPV-C) in the immunization schedule (administered by intramuscular route) by the administration of a fraction of the full dose in two shots by intradermal route (IPV-f). The possibility of this strategy was analyzed by leaders of opinions gathered by the call of the Paraguayan Pediatric Society with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). The results of the discussion are presented in this document.

COMPARATIVE EVALUATION OF SAFETY AND IMMUNOGENICITY INACTIVATED VACCINE FOR POLYOMIELITIS PREVENTION (NETHERLANDS) AND VACCINE «IMOVAX POLIO» (FRANCE) IN CHILDREN USING TRIPLE IMMUNIZATION

Aim is comparative evaluation of the safety and immunogenicity of inactivated poliomyelitis vaccine (IPV) «Bilthoven Biologicals B.V.» (Netherlands) and «Imovax Polio» (France) with subcutaneous and intramuscular modes of administration. Materials and methods. In a doubleblind, comparative clinical randomized multicenter study, 120 children at the age of 3 months participated as volunteers. They were divided into 4 groups: 1 and 2 groups were given IPV intramuscular (group 1) and subcutaneous (group 2) mode of administration, children of groups 3 and 4 were given the vaccine «Imovax Polio». Results. IPV is characterized by a high safety profile and immunogenicity both in subcutaneous and intramuscular modes of administration and it is comparable in its characteristics with the vaccine «Imovax Polio». Conclusion. Vaccine IPV (Netherlands) is recommended for registration in the territory of the Russian Federation and its further using in the National Vaccination Schedule.

Comparing the immunogenicity and safety of sequential inoculation of sIPV followed by bOPV (Ⅰ+Ⅲ) in different dosage forms

Objective: To compare the safety and immunogenicity of two different sequential schedules of inactivated poliomyelitis vaccine made from Sabin strain (sIPV) followed by typeⅠ+Ⅲ bivalent oral poliovirus vaccine (bOPV) in Drug Candy (DC) form or liquid dosage form). Methods: This randomized, blinded, single center, parallel-group controlled trial was done from September 2015 to June 2016 in Liuzhou, Guangxi province. Healthy infants aged ≥2 months were eligible for enrollment and divided into 1sIPV+2bOPV or 2sIPV+1bOPV sequential schedules. According to the bOPV dosage form each sequential schedules, the subjects again were divided into drug candy(DC) form or liquid dosage form group, being 1sIPV+bOPV (DC)/1sIPV+2bOPV(liquid)/2sIPV+1bOPV(DC)/2sIPV+1bOPV(liquid). According to 0, 28, 56 d immunization schedule, Each group were given 3 doses. We recorded adverse events during the clinical trial (399 participants who receive at least one dose). 28 days post-Dose 3, we receive a total of 350 blood samples (excluding the quitters or subjects against trial plan), using cell culture trace against polio virus neutralization test Ⅰ, Ⅱ, Ⅲ neutralizing antibody (GMT), calculating the antibody positive rate.PolioⅠ,Ⅱand Ⅲ antibody titers were assessed by virus-neutralizing antibody assay and the seroconversion (4-fold increase in titer) from pre-Dose 1 to 28 days post-Dose 3 was calculated (total 350 samples) . Results: During the vaccination, the incidence of AEs in 1sIPV+2bOPV(DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV(DC), 2sIPV+1bOPV (liquid) group were 79%, 76%, 80% and 74% (χ(2)=1.23, P=0.747) , respectively. The severe AEs in groups were 6%, 5%, 6% and 4% (χ(2)=0.57, P=0.903) , respectively, and none was considered to be vaccination related. 28 days after 3(rd) vaccination, the seroconversion rates in 1sIPV+2bOPV (DC), 1sIPV+2bOPV (liquid), 2sIPV+1bOPV (DC), 2sIPV+1bOPV (liquid) group, were 99%, 100%, 99% and 99% (χ(2)=0.94, P=0.815) , respectively, for type Ⅰ poliovirus; and 47%, 57%, 80%, 79% (χ(2)=31.56, P<0.001) , respectively, for type Ⅱ; and were 100%, 99%, 100%, 99% (χ(2)=2.02, P=0.568) , respectively, for type Ⅲ. In each group, the GMT of antibody against poliovirus typeⅠ were 4 539.68, 6 243.43, 6 819.53 and 7 916.29 (F=25.87, P<0.001) , respectively; Type Ⅱ were 12.98, 10.54, 63.75 and 84.21 (F=8.68, P=0.034) , respectively; Type Ⅲ were 1 172.55, 1 416.03, 2 648.89 and 3 250.75 (F=14.50, P=0.002) , respectively. Conclusion: On the same sequential schedules, there was no significant difference between the dosage forms, all of them showed good safety and immunogenicity. In the same dosage forms with different sequential schedules, the seroconversion rate was higher in 2 dose sIPV group than the 1 dose sIPV group, especially at the neutralizing antibody GMT level against polio type Ⅱ and Ⅲ after vaccination.

Cardio-respiratory Events and Inflammatory Response After Primary Immunization in Preterm Infants < 32 Weeks Gestational Age: A Randomized Controlled Study.

Inflammation may depress respiration in neonates. This study aimed to establish a link between postimmunization inflammation and cardio-respiratory events (CREs). Randomized double-blind controlled study of infants born < 32 weeks gestation receiving the 2 months vaccine, which comprised diphtheria and tetanus toxoids and acellular pertussis adsorbed combined with inactivated poliomyelitis vaccines and Haemophilus b conjugate and the pneumococcal conjugate 10-valent vaccines. Infants were randomized to ibuprofen treatment or a placebo group (n = 28/group). C-reactive protein (CRP) and prostaglandins E2 (PgE2) levels were assessed before and after immunization. CREs were recorded for 72 hours. Heart rate variability was assessed by polysomnography. In the placebo group, immunization was associated with significantly increased CRP levels and an increase in CRE (8.6 ± 11.1 before versus 14.0 ± 12.8 after), which did not reach statistical significance (P = 0.08), and no change in PgE2. The increase in CRP was correlated with changes in CRE (r = 0.4: P < 0.05). In the ibuprofen group, immunization significantly increased CRP levels but was not associated with change in CRE (6.7 ± 7.7 before versus 6.8 ± 9.7 after) and PgE2 levels. Comparing the groups, variation in CRE (ΔCRE before versus after immunization) was significantly lower in the ibuprofen group (0.1 ± 7.9 versus 5.4 ± 10.0 ΔCRE; P < 0.05). The first immunization of infants born < 32 weeks was associated with an increase in CRP. Ibuprofen treatment significantly attenuated the variation (Δ) in CRE following first immunization in these infants but the current study could not demonstrate an impact on CRP and PgE2 levels. The impact of anti-inflammatory treatment on antigenicity must be evaluated before their clinical use aiming at reducing CRE after immunization in preterm infants.